Population aging has emerged as a dominant global trend, accompanied by a progressive decline in physiological functions and an increasing prevalence of age-related diseases, including cardiovascular diseases, neurodegenerative disorders, and cancers (Chang et al., 2019). These issues have profound implications for both individual health and the sustainability of socio-economic systems (Chang et al., 2019). Such a demographic shift underscores the imperatives needed to extend a healthy lifespan, attenuate age-associated functional decline, and improve the quality of life for the elderly population. At the cellular level, current studies have identified several key mechanisms influencing aging and longevity, including telomere shortening, dysregulated nutrient sensing, mitochondrial dysfunction, oxidative stress, accumulating DNA damage, proteostasis disruption, and alterations in epigenetic regulation (López-Otín et al., 2023). However, the precise impact of aging on cellular functions, inter-organ communication, and stem/progenitor cell maintenance remains incompletely understood. Furthermore, the heterogeneity of aging phenotypes across different organs and cell types (Ogrodnik et al., 2024) necessitates tissue-specific investigation of the aging process at the molecular level.

Among vital organs, the liver, a central metabolic and immune organ, is indispensable for nutrient metabolism, molecular synthesis, detoxification, and immune modulations, which are critical in maintaining physical health. However, the liver is also susceptible to aging, manifested by pronounced morphological and physiological changes, such as reduced volume, diminished blood perfusion, and excessive lipid accumulation (Maldonado-Rengel et al., 2024; Seo et al., 2019). Notably, liver aging is intricately linked to the development and progression of liver diseases such as metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis, and hepatocellular carcinoma (HCC) (Aravinthan et al., 2013b; Bonnet et al., 2022; Guzmán et al., 2024; Jun et al., 2024; Wandrer et al., 2018; Zhang et al., 2020; Zhou et al., 2023). In addition, the aged liver exhibits impaired regenerative capacity, where hepatocytes with reduced proliferative potential compromise liver function recovery, thereby adversely affecting the prognosis of extrahepatic diseases and impeding the patient's physical health (Maeso-Díaz et al., 2022). Interestingly, however, under certain circumstances, hepatic aging can exhibit protective effects. For instance, inducing premature senescence in activated hepatic stellate cells (HSCs) significantly attenuates the progression of liver fibrosis (Kim et al., 2013).

These findings highlight the complexity of liver aging in disease progression, emphasizing the need to elucidate its mechanisms and effects to identify novel therapeutic targets and optimal intervention strategies. In this review, we systematically summarize the key features and drivers of liver aging, explore its role in various pathophysiological events and diseases, especially liver-related diseases, and consolidate existing interventions targeting liver aging. Our goal is to provide a comprehensive framework to guide future research and advance the development of targeted therapies in this vital field.